scholarly journals High-Resolution Structure of the Nuclease Domain of the Human Parvovirus B19 Main Replication Protein NS1

2021 ◽  
Author(s):  
Nancy Horton ◽  
Jonathan L Sanchez ◽  
Niloofar Ghadirian
Keyword(s):  
Dna Cleavage ◽  
Parvovirus B19 ◽  
Three Dimensional ◽  
Replication Protein ◽  
Dimensional Structure ◽  
Sequence Variant ◽  
Human Parvovirus B19 ◽  
Origin Of Replication ◽  
Viral Origin ◽  
Double Stranded Dna

Two new structures of the N-terminal domain of the main replication protein, NS1, of Human Parvovirus B19 (B19V) are presented. This domain (NS1-nuc) plays an important role in the “rolling hairpin” replication of the single-stranded B19V DNA genome, recognizing origin of replication sequences in double-stranded DNA, and cleaving (i.e. nicking) single-stranded DNA at a nearby site known as the trs. One structure of NS1-nuc is solved to 2.4 Å and shows the positions of two bound phosphate ions. A second structure shows the position of a single divalent cation in the DNA nicking active site. The three-dimensional structure of NS1-nuc is well conserved between the two forms, as well as with a previously solved structure of a sequence variant of the same domain, however shown here at significantly higher resolution. Using structures of NS1-nuc homologues bound to single- and double-stranded DNA, models for DNA recognition and nicking by B19V NS1-nuc are presented which predict residues important for DNA cleavage and for sequence specific recognition at the viral origin of replication.

scholarly journals The human parvovirus B19 non-structural protein 1 N-terminal domain specifically binds to the origin of replication in the viral DNA

Virology ◽  
2014 ◽  
Vol 449 ◽  
pp. 297-303 ◽  
Author(s):  
Sunil Kumar Tewary ◽  
Haiyan Zhao ◽  
Xuefeng Deng ◽  
Jianming Qiu ◽  
Liang Tang
Keyword(s):  
Parvovirus B19 ◽  
Human Parvovirus B19 ◽  
Origin Of Replication ◽  
Structural Protein ◽  
Viral Dna ◽  
Terminal Domain

Supercoils in human DNA

1975 ◽  
Vol 19 (2) ◽  
pp. 261-279
Author(s):  
P.R. Cook ◽  
I.A. Brazell
Keyword(s):  
Gamma Rays ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Hydrodynamic Properties ◽  
Dna Molecule ◽  
Double Stranded Dna ◽  
Human Dna ◽  
Nuclear Structures ◽  
Intercalating Agents ◽  
Characteristic Manner

The three-dimensional structure of a double-stranded DNA molecule may be described by distinguishing the helical turns of the DNA duplex from any superhelical turns that might be superimposed upon the duplex turns. There are characteristic changes in the hydrodynamic properties of superhelical DNA molecules when they interact with intercalating agents. The hydrodynamic properties of nuclear structures released by gently lysing human cells are changed by intercalating agents in this characteristic manner. The characteristic changes are abolished by irradiating the cells with gamma-rays but may be restored by incubating the cells at 37 degrees C after irradiation. These results are interpreted as showing that human DNA is supercoiled. A model for the structure of the chromosome is suggested.

scholarly journals The Symmetrical Wave Pattern of Base-Pair Substitution Rates across theEscherichia coliChromosome Has Multiple Causes

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Brittany A. Niccum ◽  
Heewook Lee ◽  
Wazim MohammedIsmail ◽  
Haixu Tang ◽  
Patricia L. Foster
Keyword(s):  
Escherichia Coli ◽  
Error Correction ◽  
Base Pair ◽  
Three Dimensional ◽  
Wave Pattern ◽  
Mutation Rates ◽  
Dimensional Structure ◽  
Origin Of Replication ◽  
Content Type ◽  
Eukaryotic Genomes

ABSTRACTMutation accumulation experiments followed by whole-genome sequencing have revealed that, for several bacterial species, the rate of base-pair substitutions (BPSs) is not constant across the chromosome but varies in a wave-like pattern that is symmetrical about the origin of replication. The experiments reported here demonstrated that, inEscherichia coli, several interacting factors determine the wave. The origin is a major driver of BPS rates. When it is relocated, the BPS rates in a 1,000-kb region surrounding the new origin reproduce the pattern that surrounds the normal origin. However, the pattern across distant regions of the chromosome is unaltered and thus must be determined by other factors. Increasing the deoxynucleoside triphosphate (dNTP) concentration shifts the wave pattern away from the origin, supporting the hypothesis that fluctuations in dNTP pools coincident with replication firing contribute to the variations in the mutation rate. The nucleoid binding proteins (HU and Fis) and the terminus organizing protein (MatP) are also major factors. These proteins alter the three-dimensional structure of the DNA, and results suggest that mutation rates increase when highly structured DNA is replicated. Biases in error correction by proofreading and mismatch repair, both of which may be responsive to dNTP concentrations and DNA structure, also are major determinants of the wave pattern. These factors should apply to most bacterial and, possibly, eukaryotic genomes and suggest that different areas of the genome evolve at different rates.IMPORTANCEIt has been found in several species of bacteria that the rate at which single base pairs are mutated is not constant across the genome but varies in a wave-like pattern that is symmetrical about the origin of replication. UsingEscherichia colias our model system, we show that this pattern is the result of several interconnected factors. First, the timing and progression of replication are important in determining the wave pattern. Second, the three-dimensional structure of the DNA is also a factor, and the results suggest that mutation rates increase when highly structured DNA is replicated. Finally, biases in error correction, which may be responsive both to the progression of DNA synthesis and to DNA structure, are major determinants of the wave pattern. These factors should apply to most bacterial and, possibly, eukaryotic genomes and suggest that different areas of the genome evolve at different rates.

scholarly journals Biochemical features of parvovirus B19 genovariant 1a2 dominating during the incidence rise in Belarus

2020 ◽  
Vol 17 (2) ◽  
pp. 211-220
Author(s):  
M. A. Yermalovich ◽  
V. V. Khrustalev ◽  
T. A. Khrustaleva ◽  
V. V. Poboinev ◽  
E. O. Samoilovich
Keyword(s):  
Amino Acid ◽  
Parvovirus B19 ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Dimensional Structure ◽  
Amino Acid Substitutions ◽  
Structural Protein ◽  
Mutational Pressure ◽  
Amino Acid Variability ◽  
Unique Amino Acid

Two genovariants (1a1 and 1a2) are distinguished among Human parvovirus B19 (B19P) of subgenotype 1a, of which 1a2 was predominantly distributed during the incidence rise in Belarus. The aim of this study was a comparative analysis of the amino acid variability and of the mutational pressure directions in different parts of the genome between genovariants 1a1 and 1a2.The analysis of the consensus amino acid sequences of two genovariants and the three-dimensional structure models of protein fragments was carried out. In total, two unique amino acid substitutions in the main non-structural protein NS1 of 1a2 were found (I181M and E114G), one of which E114G is close to the DNA-binding domain (OBD) responsible for attachment to the replication origin site and can affect the rate of virus replication and transcription. Three unique amino acid substitutions were found in the structural polypeptide VP of 1a2: V30L, S98N, and N533S. Two of them are located in the most immunogenic region VP1u and can contribute to the escape from immune response. The investigation of the mutational pressure direction revealed a decrease in the frequency of G to T transversions in the second reading frame of 1a2, which reflects a higher transcription rate as a result of amino acid substitution in the OBD protein.The differences revealed between the genetic variants of subgenotype 1a B19P both in the antigenic sites and in the replication and transcription system can provide an increased “fitness” for the genetic variant 1a2 and explain its predominant distribution during the incidence rise.

scholarly journals Denaturation of the simian virus 40 origin of replication mediated by human replication protein A.

1997 ◽  
Vol 17 (7) ◽  
pp. 3876-3883 ◽  
Author(s):  
C Iftode ◽  
J A Borowiec
Keyword(s):  
Protein A ◽  
Simian Virus 40 ◽  
Replication Protein A ◽  
Simian Virus ◽  
T Antigen ◽  
Replication Protein ◽  
Origin Of Replication ◽  
Sv40 T Antigen ◽  
Viral Origin ◽  
Single Stranded Dna

The initiation of simian virus 40 (SV40) replication requires recognition of the viral origin of replication (ori) by SV40 T antigen, followed by denaturation of ori in a reaction dependent upon human replication protein A (hRPA). To understand how origin denaturation is achieved, we constructed a 48-bp SV40 "pseudo-origin" with a central 8-nucleotide (nt) bubble flanked by viral sequences, mimicking a DNA structure found within the SV40 T antigen-ori complex. hRPA bound the pseudo-origin with similar stoichiometry and an approximately fivefold reduced affinity compared to the binding of a 48-nt single-stranded DNA molecule. The presence of hRPA not only distorted the duplex DNA flanking the bubble but also resulted in denaturation of the pseudo-origin substrate in an ATP-independent reaction. Pseudo-origin denaturation occurred in 7 mM MgCl2, distinguishing this reaction from Mg2+-independent DNA-unwinding activities previously reported for hRPA. Tests of other single-stranded DNA-binding proteins (SSBs) revealed that pseudo-origin binding correlates with the known ability of these SSBs to support the T-antigen-dependent origin unwinding activity. Our results suggest that hRPA binding to the T antigen-ori complex induces the denaturation of ori including T-antigen recognition sequences, thus releasing T antigen from ori to unwind the viral DNA. The denaturation activity of hRPA has the potential to play a significant role in other aspects of DNA metabolism, including DNA repair.

scholarly journals Human Bocavirus Capsid Structure: Insights into the Structural Repertoire of the Parvoviridae

2010 ◽  
Vol 84 (12) ◽  
pp. 5880-5889 ◽  
Author(s):  
Brittney L. Gurda ◽  
Kristin N. Parent ◽  
Heather Bladek ◽  
Robert S. Sinkovits ◽  
Michael A. DiMattia ◽  
...  
Keyword(s):  
Parvovirus B19 ◽  
Three Dimensional ◽  
Surface Topology ◽  
Dimensional Structure ◽  
Human Bocavirus ◽  
Dna Viruses ◽  
Variable Surface ◽  
Antigenic Properties ◽  
Α Helix ◽  
Tract Infections

ABSTRACT Human bocavirus (HBoV) was recently discovered and classified in the Bocavirus genus (family Parvoviridae, subfamily Parvovirinae) on the basis of genomic similarity to bovine parvovirus and canine minute virus. HBoV has been implicated in respiratory tract infections and gastroenteric disease in children worldwide, yet despite numerous epidemiological reports, there has been limited biochemical and molecular characterization of the virus. Reported here is the three-dimensional structure of recombinant HBoV capsids, assembled from viral protein 2 (VP2), at 7.9-Å resolution as determined by cryo-electron microscopy and image reconstruction. A pseudo-atomic model of HBoV VP2 was derived from sequence alignment analysis and knowledge of the crystal structure of human parvovirus B19 (genus Erythrovirus). Comparison of the HBoV capsid structure to that of parvoviruses from five separate genera demonstrates strong conservation of a β-barrel core domain and an α-helix, from which emanate several loops of various lengths and conformations, yielding a unique surface topology that differs from the three already described for this family. The highly conserved core is consistent with observations for other single-stranded DNA viruses, and variable surface loops have been shown to confer the host-specific tropism and the diverse antigenic properties of this family.

scholarly journals Three-Dimensional Structure of Aleutian Mink Disease Parvovirus: Implications for Disease Pathogenicity

1999 ◽  
Vol 73 (8) ◽  
pp. 6882-6891 ◽  
Author(s):  
Robert McKenna ◽  
Norman H. Olson ◽  
Paul R. Chipman ◽  
Timothy S. Baker ◽  
Tim F. Booth ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Parvovirus B19 ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Minute Virus Of Mice ◽  
Image Reconstruction Techniques ◽  
Three Dimensional Structure ◽  
Feline Panleukopenia Virus

ABSTRACT The three-dimensional structure of expressed VP2 capsids of Aleutian mink disease parvovirus strain G (ADVG-VP2) has been determined to 22 Å resolution by cryo-electron microscopy and image reconstruction techniques. A structure-based sequence alignment of the VP2 capsid protein of canine parvovirus (CPV) provided a means to construct an atomic model of the ADVG-VP2 capsid. The ADVG-VP2 reconstruction reveals a capsid structure with a mean external radius of 128 Å and several surface features similar to those found in human parvovirus B19 (B19), CPV, feline panleukopenia virus (FPV), and minute virus of mice (MVM). Dimple-like depressions occur at the icosahedral twofold axes, canyon-like regions encircle the fivefold axes, and spike-like protrusions decorate the threefold axes. These spikes are not present in B19, and they are more prominent in ADV compared to the other parvoviruses owing to the presence of loop insertions which create mounds near the threefold axes. Cylindrical channels along the fivefold axes of CPV, FPV, and MVM, which are surrounded by five symmetry-related β-ribbons, are closed in ADVG-VP2 and B19. Immunoreactive peptides made from segments of the ADVG-VP2 capsid protein map to residues in the mound structures. In vitro tissue tropism and in vivo pathogenic properties of ADV map to residues at the threefold axes and to the wall of the dimples.

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